AN EXTENDED BETA-STRAND MIMIC FOR A LARGER ARTIFICIAL BETA-SHEET

This paper reports the development of beta-strand mimic B, which dupli cates the hydrogen-bonding functionality of one edge of a tetrapeptide beta-strand. When attached to a tripeptide by a suitable Linking grou p, beta-strand mimic B forms a hydrogen-bonded antiparallel beta-sheet structure, artificial beta-sheet 2. beta-Strand mimic B is based upon a 5-hydrazino-2-methoxybenzoic acid building block. The first half of the paper describes synthetic, IR and H-1 NMR spectroscopic, X-ray cr ystallographic, and molecular modeling studies of 5-hydrazino-2-methox ybenzoic acid derivatives and related molecules. These studies establi sh that hydrazide derivatives of 5-hydrazino-2-methoxybenzoic acid ado pt a conformation similar to that of a peptide beta-strand and are sui table for use as beta-strand mimics. The second half of the paper desc ribes synthetic and H-1 NMR spectroscopic studies of artificial beta-s heet 2 and of controls 20 and 21, which resemble the peptidomimetic an d peptide strands of 2. These experiments indicate that 2 adopts a con formation and hydrogen-bonding pattern similar to that of an antiparal lel beta-sheet and establish that beta-strand mimic B can induce beta- sheet formation in an attached peptide strand.